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New Neurons in Adult Brain Buffer Stress

August 16, 2011 • Science Update

New neurons growing in the adult brain help buffer the effects of stress, according to a new study in mice. Previous research has suggested that the growth of new neurons, or neurogenesis, in adults is involved in recovery from depression. This work provides evidence that loss of new neurons plays a role in the development of depression and suggests that the stress response is the link between adult neurogenesis and depressive illness.

Background

Research has generated provocative clues that changes in the growth of new neurons in the adult brain are centrally involved in the development of, and treatment for, depression. One of the areas of the brain in which neurogenesis is known to occur, the hippocampus, has a well known role in learning and memory, but it also helps regulate the stress response. Studies have shown that stress, a known risk factor for depression, and the hormones released as a result of stressful experiences, reduce the rate of neurogenesis in the hippocampus. Other studies have found that currently available antidepressants augment neurogenesis, as does exercise, which has been shown to increase resilience to stress.

On the other hand, while there has been much evidence pointing to a link between neurogenesis and depression, studies also report that animals in which neurogenesis has been prevented by various means do not develop behavior analogous to depression. This suggested that altered neurogenesis didn’t directly cause depression; the NIMH research was aimed at exploring the connection.

This Study

In this study, reported in the journal Nature, NIMH intramural scientists led by Heather Cameron interrupted adult neurogenesis in mice, then tracked how the mice responded to stress.

Testing pointed to an impaired ability by the mice to respond to stress when neurogenesis was absent. In a first test, the investigators used gene transfer to render newly growing neurons sensitive to an antiviral drug, so that newly dividing, but not mature neurons, are eliminated. They then compared how mice with and without adult neurogenesis responded to being restrained, a stressor for mice. Immediately after the restraint ended, both groups of mice had similar levels of the hormone corticosterone, a marker of stress. Thirty minutes later, however, corticosterone was still elevated in the mice without adult neurogenesis, suggesting that their ability to recover from stress was compromised. In addition, the investigators showed that it was neurogenesis specifically in the hippocampus and not other areas of the brain that altered the response to stress.

In another standard test of depression-like behavior, which reliably shows the effects of antidepressants on behavior, the mice were offered food but had to venture into an open, exposed space to get it. Mice that had not been subjected to stress responded similarly whether or not neurogenesis was intact. If the mice were first stressed by being restrained, however, those in which neurogenesis was impaired took longer to eat, preferring safety to food. These and other tests suggested that the presence or absence of neurogenesis affected how the mice responded to stress, both in terms of internal hormonal responses and behavior.

Significance

Stress is a key risk factor for depression, but some people seem especially vulnerable to stress while others are resilient. Previous research has shown that the hippocampus is involved in regulation of the stress response system and that stress impairs neurogenesis in the hippocampus. This work suggests that adult neurogenesis helps an individual weather stress. Thus stress itself could lead to a self-reinforcing cycle leading towards a declining ability to respond effectively to stress, in some cases leading to depression. Understanding how adult neurogenesis is involved in the development of depression—and how it is involved in the actions of antidepressant medications and other therapeutic and preventive approaches—can help inform the development of new ways to prevent and treat depression.